1. Departments of Anesthesiology, St Louis, Missouri 63110, USA
2. Departments of Cell Biology and Physiology, St Louis, Missouri 63110, USA
3. Departments of Anatomy and Neurobiology, Washington University in St Louis, St Louis, Missouri 63110, USA

Correspondence to: Min Zhuo^1,3 Correspondence and requests for materials should be addressed to M.Z. (e-mail: Email: zhuom@morpheus.wustl.edu).

Abstract

Glutamate, the major excitatory neurotransmitter in the central nervous system, activates three different receptors that directly gate ion channels, namely receptors for AMPA (-amino-3-hydroxy-5-methyl isoxozole propionic acid), NMDA (N-methyl-D-aspartate), and kainate, a structural analogue of glutamate. The contribution of AMPA and NMDA receptors to synaptic transmission and plasticity is well established¹. Recent work on the physiological function of kainate receptors has focused on the hippocampus², where repetitive activation of the mossy-fibre pathway generates a slow, kainate-receptor-mediated excitatory postsynaptic current (EPSC)^{3, 4, 5}. Here we show that high-intensity single-shock stimulation (of duration 200 microseconds) of primary afferent sensory fibres produces a fast, kainate-receptor-mediated EPSC in the superficial dorsal horn of the spinal cord. Activation of low-threshold afferent fibres generates typical AMPA-receptor-mediated EPSCs only, indicating that kainate receptors may be restricted to synapses formed by high-threshold nociceptive (pain-sensing) and thermoreceptive primary afferent fibres. Consistent with this possibility, kainate-receptor-mediated EPSCs are blocked by the analgesic -opiate-receptor agonist Damgo and spinal blockade of both kainate and AMPA receptors produces antinociception. Thus, spinal kainate receptors contribute to transmission of somatosensory inputs from the periphery to the brain.